Ocular surface diseases, affecting the corneal and conjunctival epithelia and immediately subjacent tissues, are among the most difficult external eye diseases to treat. The overall goals of this grant are to improve our understanding of the normal and diseased conjunctival and corneal epithelia (the ocular surface epithelium) with the eventual aim being the ability to define and manipulate some of the factors responsible for ocular surface disease. The first specific aim of the grant is to study the healing, replication, mucin production, and goblet cell status of the conjunctiva in normal and diseased eyes. This will be done using rabbit and human tissue. Healing will be studied in vivo by planimetry, and by histology. Replication, mucin production, and goblet cell status will be studied in conjunctival biopsies using organ culture and histological techniques. The second major aim is to study the acute transformation of conjunctival to corneal epithelium by evaluating the completeness of transformation as a function of time in rabbits, and by determining whether a similar process of transformation occurs in rats. Third, we will study the role of conjunctiva in the normal maintenance of corneal epithelium by evaluating clinically and histologically the effect of conjunctival injury on the corneal epithelium in vivo in rabbits. Fourth, we will continue studies of the metabolism of the corneal epithelium in response to stress. Finally, special attention will be directed to studies of persistent epithelial defect, a serious complication of many ocular surface disorders. The nature of the cell and substrate surfaces will be analysed immunohistochemically in tissues from patients with epithelial defects, and the results of those studies will be correlated with the clinical characteristics of the defects. Also, we will attempt to develop an animal model of persistent epithelial defect by combining a traumatic with a metabolic insult. By such studies, we hope to be able to define and manipulate some of the factors responsible for ocular surface disease.